Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease

Hamilton, Laura; Dufresne, Martin; Joppé, Sandra E.; Petryszyn, Sarah; Aumont, Anne; Calon, Frédéric; Barnabé-Heider, Fanie; Fürtös, Alexandra; Parent, Martin; Chaurand, Pierre; Fernandes, Karl J.L.

doi:10.1016/j.stem.2015.08.001

Cited by 218 publications

(228 citation statements)

References 75 publications

(86 reference statements)

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“…We investigated the distribution of lactate within E9.5 embryos using matrix-assisted laser desorption/ ionization-imaging mass spectrometry (MALDI-IMS), a useful method for visualizing the spatial distribution of individual biomolecules at a spatial resolution of ∼30 µm pitch on intact tissues (Bailey et al, 2015;Hamilton et al, 2015;Sugiura et al, 2014). Fresh frozen embryos were sectioned and analyzed by MALDI-IMS.…”

Section: Transition Of Embryonic Metabolome Profiles During Cbmentioning

confidence: 99%

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Miyazawa¹,

Yamaguchi²,

Honda³

et al. 2017

Journal of Cell Science

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Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development.

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Section: Transition Of Embryonic Metabolome Profiles During Cbmentioning

confidence: 99%

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Miyazawa¹,

Yamaguchi²,

Honda³

et al. 2017

Journal of Cell Science

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“…Recent research (POLO-HERNANDEZ et al, 2014;ASTARITA et al, 2011;HAMILTON et al, 2015) has focused on the importance of oleic acid in the modulation mechanism of neural stem cell (NSC) transformation in neurons, neuron migration and synapse formation.…”

Section: Sgarbieri V C; Pacheco M T Bmentioning

confidence: 99%

“…Some lines of evidence have shown the occurrence of increased expression of the enzyme stearoyl-CoA-desaturase (SCD) in AD (ASTARITA et al, 2011). Hamilton et al (2015) identified a focus of lipid metabolism deregulation as a blocking mechanism in the reproduction of neural stem cells (NSC), resulting from Alzheimer's disease (AD). The authors demonstrated that interference in the signaling or synthesis of oleic acid blocked the proliferation of neural stem cells (NSC) in mouse models for AD.…”

Section: Sgarbieri V C; Pacheco M T Bmentioning

confidence: 99%

Premature or pathological aging: longevity

Sgarbieri

Pacheco

2017

Braz. J. Food Technol.

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The main objective of this literature review was to summarize and characterize the main factors and events that may negatively influence quality of life and human longevity. The factors that act on premature aging processes are essentially the same as those of natural or healthy aging, but in a more intense and uncontrolled manner. Such factors are: 1) genetic (genome); 2) metabolic (metabolome); 3) environmental (life conditions and style, including diet). Factors 1 and 2 are more difficult to control by individuals; once depending on socioeconomic, cultural and educational conditions. Differently of environmental factors that may be totally controlled by individuals. Unfamiliarity with these factors leads to chronic and/or degenerative diseases that compromise quality of life and longevity.Keywords: Human longevity; Metabolic changes; Aging; Life quality; Diet. ResumoO principal objetivo desta revisão da literatura foi resumir e caracterizar os principais fatores e eventos que podem influenciar negativamente a qualidade de vida e a longevidade humana. Os fatores que atuam nos processos de envelhecimento prematuro são essencialmente os mesmos que aqueles relacionados ao envelhecimento saudável ou natural, mas em uma maior intensidade ou maneira descontrolada. Tais fatores são: 1) genéticos (genoma); 2) metabólicos (metaboloma); 3) ambientais (condições e estilos de vida, incluindo a alimentação). Os fatores dos itens 1 e 2 são mais difíceis de ser controlados, pois dependem das condições socioeconômicas, culturais e educacionais. Diferentemente dos fatores ambientais que podem ser controlados pelo indivíduo. A falta de familiaridade com esses fatores leva a doenças crônicas e/ou degenerativas que comprometem a qualidade de vida e a longevidade. Palavras-chave:Longevidade; Alterações metabólicas; Envelhecimento; Qualidade de vida; Alimentação.

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“…Continuing with this theme, Karl Fernandes (University of Montreal, Canada) showed that ependymal cells at the interface between the brain and cerebrospinal fluid (CSF) accumulate neutral lipids in Alzheimer's disease (Hamilton et al, 2015). The aberrant lipid droplet accumulation at the brain-CSF interface triggers the deterioration of the surrounding neural stem cell niche.…”

Section: Lipids and Neurodegenerationmentioning

confidence: 99%

Meeting report – Emerging Concepts in Cell Organization

Teis

Kukulski

2017

Journal of Cell Science

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New concepts in cell organization emerged in a medieval castle during a snowy week in January 2017 in the middle of the Austrian Alps. The occasion was the 10th Annaberg EMBO workshop in Goldegg am See; organized by Gabriele Seethaler, Catherine Rabouille and Marino Zerial. There were 95 participants, including many who gave talks and presented posters, enjoying a familial and trusting atmosphere that stimulated lively exchange of (unpublished) results, new ideas and thoughts.As at previous occasions when this community met in the same spot, the aim of the meeting was to identify the key questions in cell biology and set the ground for future research directions. The inspirational character of the meeting and the enthusiasm of the participants certainly achieved that. The new concepts that emerged will be shaping our understanding of how cells are organized and how this organization impacts cellular functions. Overall, it became clear that there is a discrepancy between the textbook views of the cellular building plan and how the field currently envisions a cell is really built. Furthermore, novel methods allow the study of the complexity of cellular organization, and old methods are being revisited. This report is an attempt to recapitulate and integrate the ideas that emerged at the workshop, and thereby provide inspiration to the larger community. All presentations and, in particular the lively poster sessions, were essential for the success of the meeting. However, owing to space restrictions, we could not cover all short talks or the posters here. We apologize to our colleagues whose presentations could not be discussed here.Secretion: making proteins and membranes and how to get them out A lot remains to be discovered about intra-organelle communication by 'classical' vesicular trafficking, especially in the secretory pathway. For instance, how do cells ensure that vesicles contain the right cargo? Liz Miller (MRC LMB, Cambridge, UK) explained protein quality control at endoplasmic reticulum (ER) exit sites and presented a cargo-crowding mechanism that helps to exclude ER-resident proteins from being packed into COPII vesicles, thereby preventing their 'spilling over' into the Golgi.While ER export has been intensely studied, exit sites from the trans-Golgi network (TGN) have remained more elusive. Stéphanie Miserey-Lenkei (Institut Curie, Paris, France) highlighted that RAB6 controls membrane fission of transport vesicles at the TGN through coupling motor proteins of the kinesin and myosin family to the cytoskeleton at specific sites of fission. This coupling ensures the spatial coordination between the fission of RAB6-positive vesicles and their exit along microtubules (Miserey-Lenkei et al., under review).Another important question is how is specificity in trafficking to and through the Golgi achieved? After all, the Golgi is the major protein distribution center of the cell. Sean Munro (MRC LMB, Cambridge, UK), this year's winner of the famous Grunzelsbacher award (sponsored by the elusive Aus...

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Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease

Cited by 218 publications

References 75 publications

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

Premature or pathological aging: longevity

Meeting report – Emerging Concepts in Cell Organization

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